Mechanisms of steroid-triggered cell death in Drosophila

描述(由申请人提供) 类固醇激素是所有高等细胞程序性死亡的关键调节因素 有机体。然而，尽管它们在这一进程中发挥了核心作用， 类固醇激素调节细胞死亡的机制尚不清楚。这里, 提出了一种正向遗传策略来研究一个戏剧性的例子 类固醇引发的细胞死亡：幼虫的大规模和快速破坏 果蝇变态过程中的组织对类固醇激素的反应 蜕皮激素。为此，开发了一种简单的检测方法来监测幼虫 活体动物的唾液腺。破坏幼虫唾液腺的突变 细胞死亡将被选择，只有那些导致阻止 死亡反应，而不是那些扰乱蜕皮激素信号的反应，将是 进一步刻画的。基因策略从来没有被用来研究 荷尔蒙在任何有机体中都会引发细胞死亡。这些研究将不会提供 只有更好地理解程序化细胞的激素调节 死亡，但也将作为一个模型系统，了解如何系统性 激素信号被提炼成特定阶段和特定组织的生物信号 在开发过程中的响应。此外，还进一步表征了 细胞凋亡信号通路将有助于更好地理解自身免疫 疾病、神经退行性疾病和其他由以下原因引起的疾病 对程序性细胞死亡的错误调控。

DESCRIPTION (provided by applicant) Steroid hormones are critical regulators of programmed cell death in all higher organisms. In spite of their central role in this process, however, the mechanisms by which steroid hormones regulate cell death remain unclear. Here, a forward genetic strategy is proposed to study a dramatic example of steroid-triggered cell death: the massive and rapid destruction of larval tissues during Drosophila metamorphosis in response to the steroid hormone ecdysone. To this end, a simple assay has been developed to monitor larval salivary glands in living animals. Mutations that disrupt larval salivary gland cell death will be selected and only those mutations that result in a block of the death response, rather than those that disrupt the ecdysone signal, will be further characterized. A genetic strategy has never been used to study hormone-triggered cell death in any organism. These studies will provide not only a better understanding of the hormonal regulation of programmed cell death, but will also serve as a model system for understanding how systemic hormonal signals are refined into stage- and tissue-specific biological responses during development. In addition, further characterization of apoptotic signaling pathways will allow a better understanding of autoimmune diseases, neurodegenerative disorders, and other diseases that result from misregulation of programmed cell death.